DNMT3A (DNA methyltransferase 1)

The data give insight into how DNA methylation patterns are established in human cells. We discuss these findings and their potential relevance for altered DNA methylation patterns seen in aging tissues and in cancer cells.

P2, N=80, Recruiting, Mayo Clinic | Trial completion date: Mar 2026 --> Nov 2033 | Trial primary completion date: Dec 2025 --> Feb 2031

In AML, it correlated with CD33 expression and inv(16)/t(16;16). In conclusion, mesothelin is rare in ALL but enriched in specific AML subtypes and not prognostic for survival.

This case represents a rare pcTFH-PTCL with a persistent T-cell clone coexisting with divergent clonal B- and plasma cell populations. The findings emphasize the role of TFH-derived neoplasms in fostering B-cell expansions and highlight the diagnostic and therapeutic complexity posed by dual-lineage clonality in cutaneous lymphomas.

We also investigated loci previously associated with risk of clonal hematopoiesis (CH) or clonal hematopoiesis of indeterminate potential (CHIP) and identified several variants associated with risk of AML. Our results further inform on AML etiology and demonstrate the existence of disease sub-group specific risk loci.

AML with HOXB3 hypomethylation usually has unique genetic patterns such as a normal karyotype, cytogenetic/molecular-intermediate risk, and mutations in FLT3-ITD, NPM1 and DNMT3A. Despite these associations, HOXB3 hypomethylation may serve as an independent prognostic biomarker for AML.

Multivariate analysis confirmed high bZIP-domain VAF and DNMT3A mutation as independent risk factors. Our results confirm that the bZIP-domain VAF of CEBPA mutations is a more effective predictor of relapse than the maximum VAF, offering a valuable tool for the early identification of patients at high risk of relapse.

AML with KMT2A-PTD shows distinctive immunophenotypic features with increased CD123 and aberrant CD25 expression, both associated with FLT3-ITD. These markers may have diagnostic and therapeutic relevance in this AML subtype.

This study revealed that patients aged ≥50 years displayed more complex genetic aberration profiles and experienced significantly poorer prognoses compared to their younger counterparts. These findings provided novel insights for optimizing treatment strategies for middle-aged and elderly AML patients in the Chinese population.

According to previous reports, lymphomatous effusion, which is frequently measured in months, is associated with a short survival. Based on these data and current World Health Organization (WHO) and National Comprehensive Cancer Network (NCCN) guidance, we propose a practical fluid-based diagnostic algorithm that integrates cytology, ancillary tools, and lymph node biopsy when feasible, and we highlight the need for standardized effusion-based workflows, multicenter registries, and the integration of liquid biopsies, multiomics, and artificial intelligence-assisted cytology to refine risk stratification and guide therapy in this distinct subgroup.

Our study demonstrates that patients with eAML subtype have a worse prognosis, unique molecular features and higher tumor burden. Allo-HSCT might be an effective way to improve prognosis. This study provides evidence critical for risk stratification and treatment optimization in eAML.

Efficacy of Decitabine (DCT) - a chemical analogue of AZA - was demonstrated in a subset of primary meningioma cells. Molecular impact was largely independent of DNMT expression and methylation profile. Next to inducing DNA demethylation and epigenetic reprogramming, efficacy of AZA may be due to other molecular mechanisms of action.